Wesley Elon Fleming1, Aliya Ferouz-Colborn2, Michael K Samoszuk3, Armaghan Azad4, Jiuliu Lu5, John S Riley6, Amabelle B Cruz7, Susann Podolak8, Doni J Clark9, Kurtis R Bray10, Paula C Southwick11. 1. Sleep Center Orange County, 4980 Barranca Pkwy, Ste 170, Irvine, CA 92604, USA. Electronic address: flemingwesley@gmail.com. 2. San Diego Sleep and Sinus Clinic, 477 N El Camino Real, D-308, Encinitas, CA 92024, USA. Electronic address: aliya.s.ferouz-colborn@kp.org. 3. Beckman Coulter, Inc., 250 South Kraemer Blvd, Brea, CA 92821, USA. Electronic address: mksamoszuk@beckman.com. 4. Sleep Center Orange County, 4980 Barranca Pkwy, Ste 170, Irvine, CA 92604, USA. Electronic address: armaghan23@yahoo.com. 5. Beckman Coulter, Inc., 250 South Kraemer Blvd, Brea, CA 92821, USA. Electronic address: jiuliu.lu@beckman.com. 6. Beckman Coulter, Inc., 250 South Kraemer Blvd, Brea, CA 92821, USA. Electronic address: john.riley@beckman.com. 7. Beckman Coulter, Inc., 250 South Kraemer Blvd, Brea, CA 92821, USA. Electronic address: acruz@beckman.com. 8. Sleep Center Orange County, 4980 Barranca Pkwy, Ste 170, Irvine, CA 92604, USA. Electronic address: svoyer_sleepcenteroc@hotmail.com. 9. Beckman Coulter, Inc., 250 South Kraemer Blvd, Brea, CA 92821, USA. Electronic address: djclark@beckman.com. 10. Beckman Coulter, Inc., 250 South Kraemer Blvd, Brea, CA 92821, USA. Electronic address: kurt.bray@prometheuslabs.com. 11. Beckman Coulter, Inc., 250 South Kraemer Blvd, Brea, CA 92821, USA. Electronic address: pcsouthwick@beckman.com.
Abstract
OBJECTIVE/ BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder, affecting over 100 million adults. Untreated OSA leads to serious health consequences and perturbations in endocrine, immune, inflammatory, and metabolic systems. Study objectives are to evaluate the association between OSA and biomarkers, and to test the hypothesis that a combination of markers may be useful in screening for OSA. PATIENTS/ METHODS: A multicenter trial was conducted enrolling symptomatic male patients with suspected OSA. All subjects underwent in-laboratory overnight polysomnography. A non-symptomatic control group was also obtained. Eleven biomarkers were tested: HbA1c, CRP, EPO, IL-6, uric acid, cortisol, hGH, prolactin, testosterone, DHEA (Beckman Coulter UniCel DxC 600i Synchron® Access® Clinical Systems), IGF-1. RESULTS: 73 male subjects were enrolled; 26 had moderate/severe OSA. ROC curve analysis showed HbA1c, CRP, EPO, IL-6, and Uric Acid (AUCs: 0.76, 0.73, 0.65, 0.65, 0.61) were superior to the Epworth Sleepiness Scale (AUC: 0.52). Concurrent elevation of HbA1c and CRP provide even greater predictive power. A combination of elevated HbA1c, CRP, and EPO provided 0.08 increase in AUC (0.84 [0.75 - 0.94]) over individual markers (p<0.05), with high sensitivity (85%), and specificity (79%) for moderate/severe OSA. CONCLUSIONS: OSA induces characteristic endocrine, immune, inflammatory, and metabolic disturbances that can be detected with blood biomarkers. These biomarkers are superior to standard screening questionnaires. Various clusters of these biomarkers have an even greater association with OSA and thus may represent physiologic signatures of the disorder that may have value in initial screening for OSA as well as for follow-up of therapy response.
OBJECTIVE/ BACKGROUND:Obstructive sleep apnea (OSA) is a common disorder, affecting over 100 million adults. Untreated OSA leads to serious health consequences and perturbations in endocrine, immune, inflammatory, and metabolic systems. Study objectives are to evaluate the association between OSA and biomarkers, and to test the hypothesis that a combination of markers may be useful in screening for OSA. PATIENTS/ METHODS: A multicenter trial was conducted enrolling symptomatic male patients with suspected OSA. All subjects underwent in-laboratory overnight polysomnography. A non-symptomatic control group was also obtained. Eleven biomarkers were tested: HbA1c, CRP, EPO, IL-6, uric acid, cortisol, hGH, prolactin, testosterone, DHEA (Beckman Coulter UniCel DxC 600i Synchron® Access® Clinical Systems), IGF-1. RESULTS: 73 male subjects were enrolled; 26 had moderate/severe OSA. ROC curve analysis showed HbA1c, CRP, EPO, IL-6, and Uric Acid (AUCs: 0.76, 0.73, 0.65, 0.65, 0.61) were superior to the Epworth Sleepiness Scale (AUC: 0.52). Concurrent elevation of HbA1c and CRP provide even greater predictive power. A combination of elevated HbA1c, CRP, and EPO provided 0.08 increase in AUC (0.84 [0.75 - 0.94]) over individual markers (p<0.05), with high sensitivity (85%), and specificity (79%) for moderate/severe OSA. CONCLUSIONS: OSA induces characteristic endocrine, immune, inflammatory, and metabolic disturbances that can be detected with blood biomarkers. These biomarkers are superior to standard screening questionnaires. Various clusters of these biomarkers have an even greater association with OSA and thus may represent physiologic signatures of the disorder that may have value in initial screening for OSA as well as for follow-up of therapy response.
Authors: Bharati Prasad; Alana D Steffen; Hans P A Van Dongen; Francis M Pack; Inna Strakovsky; Bethany Staley; David F Dinges; Greg Maislin; Allan I Pack; Terri E Weaver Journal: Sleep Date: 2018-02-01 Impact factor: 5.849